Lack of association of Aspergillus colonization with the development of bronchiolitis obliterans syndrome in lung transplant recipients: An international cohort study

https://doi.org/10.1016/j.healun.2019.06.007Get rights and content

BACKGROUND

Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS.

METHODS

Consecutive LTRs from January 2005 to December 2008 were evaluated. Rates of BOS and associated risk factors were recorded at 4 years. International Society of Heart and Lung Transplantation criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization and the development of BOS controlling for confounders.

RESULTS

A total of 747 LTRs were included. The cumulative incidence of BOS at 4 years after transplant was 33% (250 of 747). Additionally, 22% of LTRs experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (hazard ratio [HR] = 0.6, 95% confidence interval [CI] = 0.3–1.2, p = 0.12) or small conidia (HR = 0.9, 95% CI = 0.6–1.4, p = 0.74) was not associated with the development of BOS. Factors associated with increased risk of development of BOS were the male gender (HR = 1.4, 95% CI = 1.1–1.8, p = 0.02) and episodes of acute rejection (1–2 episodes, HR = 1.5, 95% CI = 1.1–2.1, p = 0.014; 3–4 episodes, HR = 1.6, 95% CI = 1.0–2.6, p = 0.036; >4 episodes, HR = 2.2, 95% CI = 1.1–4.3, p = 0.02), whereas tacrolimus use was associated with reduced risk of BOS (HR = 0.6, 95% CI = 0.5–0.9, p = 0.007).

CONCLUSIONS

We conclude from this large multicenter cohort of lung transplant patients, that Aspergillus colonization with large or small conidia did not show an association with the development of BOS.

Section snippets

Study design and patients

This was an international, multicenter, retrospective, non-interventional cohort study of patients who had received lung transplants. Fourteen lung transplant centers from around the globe participated, including the United States of America, Canada, France, Germany, Italy, The Netherlands, Spain, Switzerland, and Australia.

A total of 900 consecutive LTRs aged ≥18 years who underwent single lung, double lung, or heart–lung transplantation at the participating study centers from January 1, 2005

Demographics

A total of 900 LTRs were eligible for evaluation. We excluded 42 patients who received a prior lung transplant, 43 with missing BOS status, and 68 who died within 90 days of transplantation. As illustrated in Figure 1, 250 LTRs developed BOS within 4 years after transplantation, whereas 497 patients did not. Median follow-up time from lung transplantation to the end of their follow up was 3.7 years (IQR, 1.5–4.0 years). The characteristics of the cohort are described in Table 1. The mean age

Discussion

BOS is one of the leading causes of death beyond 1 year after transplant, affecting nearly half of recipients at 5 years after transplant, and 75% at 10 year after transplant.33, 34 Many factors have been reported to contribute toward BOS. However, the quality of data is often an issue, as almost all existing evidence derives from retrospective studies with no control groups and only reflects the experience of single centers. Additionally, the number of patients included were often small,

Disclosure statement

This study was funded by Pfizer. Pfizer did not have any input in the manuscript preparation and conclusion. Dr Shahid Husain has received research grants from Merck and Pfizer, educational grant from Astellas, and consultancy fees from Cidara. F.P.S. has received research support from Pfizer, Gilead, Shire, CSL Behring, Qiagen, Ansun Biopharma, and Whiscon. Drs Jay Aram and Muhammad Younus are employees of Pfizer Inc, New York, USA. L.G.S. has received research support from Gilead, and Pfizer,

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